Difference between revisions of "Colorectal cancer, HER2-positive"
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<big>Note: the page has regimens specific to Her2-amplified colon cancer. | <big>Note: the page has regimens specific to Her2-amplified colon cancer. | ||
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*See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.</big> | *See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.</big> | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
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=Guidelines= | =Guidelines= | ||
==[http://www.esmo.org/ ESMO]== | ==[http://www.esmo.org/ ESMO]== | ||
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*'''2016:''' Van Cutsem et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Management-of-Patients-with-Metastatic-Colorectal-Cancer ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.] [https://pubmed.ncbi.nlm.nih.gov/27380959 PubMed] | *'''2016:''' Van Cutsem et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Management-of-Patients-with-Metastatic-Colorectal-Cancer ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.] [https://pubmed.ncbi.nlm.nih.gov/27380959 PubMed] | ||
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===Older=== | ===Older=== | ||
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*'''2013:''' Labianca et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi64.full.pdf+html Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/24078664 PubMed] | *'''2013:''' Labianca et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi64.full.pdf+html Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/24078664 PubMed] | ||
*'''2013:''' Balmaña et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi73.full.pdf+html Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/23813931 PubMed] | *'''2013:''' Balmaña et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi73.full.pdf+html Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/23813931 PubMed] | ||
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==[http://www.jsccr.jp/en/index.html Japanese Society for Cancer of the Colon and Rectum]== | ==[http://www.jsccr.jp/en/index.html Japanese Society for Cancer of the Colon and Rectum]== | ||
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*'''2016:''' Watanabe et al. [https://doi.org/10.1007/s10147-017-1101-6 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer] [https://pubmed.ncbi.nlm.nih.gov/28349281 PubMed] | *'''2016:''' Watanabe et al. [https://doi.org/10.1007/s10147-017-1101-6 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer] [https://pubmed.ncbi.nlm.nih.gov/28349281 PubMed] | ||
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==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
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*[https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer] | *[https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer] | ||
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==[http://www.siog.org/ SIOG]== | ==[http://www.siog.org/ SIOG]== | ||
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*'''2014:''' Papamichael et al. [https://academic.oup.com/annonc/article/26/3/463/222917 Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013] | *'''2014:''' Papamichael et al. [https://academic.oup.com/annonc/article/26/3/463/222917 Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013] | ||
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=Advanced or metastatic disease, second or third-line therapy= | =Advanced or metastatic disease, second or third-line therapy= | ||
==Pertuzumab & Trastuzumab {{#subobject:ea894c|Regimen=1}}== | ==Pertuzumab & Trastuzumab {{#subobject:ea894c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
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===Regimen {{#subobject:98buya|Variant=1}}=== | ===Regimen {{#subobject:98buya|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 80%; text-align:center;" | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
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!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[https://doi.org/10.1016/S1470-2045(18)30904-5 Meric-Bernstam et al. 2019 (MyPathway)] | + | |[https://doi.org/10.1016/S1470-2045(18)30904-5 Meric-Bernstam et al. 2019 (MyPathway HER2 CRC subset)] |
|2014-2017 | |2014-2017 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
Line 54: | Line 40: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
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*HER2 amplification | *HER2 amplification | ||
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''Patients enrolled in MyPathway had ECOG 0-2'' | ''Patients enrolled in MyPathway had ECOG 0-2'' | ||
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''Diagnostic criteria for Her2 positivity in MyPathway:'' | ''Diagnostic criteria for Her2 positivity in MyPathway:'' | ||
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*Patients with solid tumors that have HER2 overexpression, amplification, or HER2-activating mutation as identified by assays performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. | *Patients with solid tumors that have HER2 overexpression, amplification, or HER2-activating mutation as identified by assays performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. | ||
**Assays using in situ hybridization (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) must indicate the presence of gene amplification with a HER2/CEP17 ratio of ≥ 2 or HER2 gene copy number > 6.0. | **Assays using in situ hybridization (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) must indicate the presence of gene amplification with a HER2/CEP17 ratio of ≥ 2 or HER2 gene copy number > 6.0. | ||
Line 67: | Line 50: | ||
**Assays using next generation sequencing (NGS) of genes with known or potentially clinically relevant alterations or analysis by real-time polymerase chain reaction (RT-PCR) must identify clinically activating mutations (those with major coding disruptions resulting in an amino acid change that is likely to be detrimental to protein function, including premature stop codons or frameshift mutations early in the coding region) or copy number gain. | **Assays using next generation sequencing (NGS) of genes with known or potentially clinically relevant alterations or analysis by real-time polymerase chain reaction (RT-PCR) must identify clinically activating mutations (those with major coding disruptions resulting in an amino acid change that is likely to be detrimental to protein function, including premature stop codons or frameshift mutations early in the coding region) or copy number gain. | ||
**In cases where multiple assays are done, HER2 positivity by any of the testing methodologies would make the patient eligible as long as eligibility criteria are fulfilled. | **In cases where multiple assays are done, HER2 positivity by any of the testing methodologies would make the patient eligible as long as eligibility criteria are fulfilled. | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
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*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
**Cycle 1: 840 mg IV once on day 1 | **Cycle 1: 840 mg IV once on day 1 | ||
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**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
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'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''MyPathway HER2 CRC subset:''' Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. Epub 2019 Mar 8. [https://doi.org/10.1016/S1470-2045(18)30904-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30857956 PubMed] NCT02091141 | |
− | #'''MyPathway:''' Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. Epub 2019 Mar 8. [https://doi.org/10.1016/S1470-2045(18)30904-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30857956 PubMed] NCT02091141 | ||
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==Lapatinib & Trastuzumab {{#subobject:e17gbc|Regimen=1}}== | ==Lapatinib & Trastuzumab {{#subobject:e17gbc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
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===Regimen {{#subobject:9817cz|Variant=1}}=== | ===Regimen {{#subobject:9817cz|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 80%; text-align:center;" | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
Line 99: | Line 78: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
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*KRAS wild-type, HER2 amplification | *KRAS wild-type, HER2 amplification | ||
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''Patients enrolled in HERACLES had ECOG 0-1'' | ''Patients enrolled in HERACLES had ECOG 0-1'' | ||
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''Diagnostic criteria for Her2 positivity in HERACLES:'' | ''Diagnostic criteria for Her2 positivity in HERACLES:'' | ||
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*Tumours with 3+ HER2 score in more than 50% of cells by immunohistochemistry | *Tumours with 3+ HER2 score in more than 50% of cells by immunohistochemistry | ||
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or | or | ||
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*2+ HER2 score and a HER2:CEP17 ratio higher than two in more than 50% of cells by FISH | *2+ HER2 score and a HER2:CEP17 ratio higher than two in more than 50% of cells by FISH | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Lapatinib (Tykerb)]] 1000 mg PO once per day | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 4 mg/kg IV once on day 1 | **Cycle 1: 4 mg/kg IV once on day 1 | ||
**Cycle 2 onwards: 2 mg/kg IV once on day 1 | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
− | |||
'''7-day cycles''' | '''7-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
#'''HERACLES:''' Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):738-746. Epub 2016 Apr 20. [https://doi.org/10.1016/S1470-2045(16)00150-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27108243 PubMed] EudraCT 2012-002128-33 | #'''HERACLES:''' Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):738-746. Epub 2016 Apr 20. [https://doi.org/10.1016/S1470-2045(16)00150-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27108243 PubMed] EudraCT 2012-002128-33 | ||
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==Trastuzumab deruxtecan monotherapy {{#subobject:ea894c|Regimen=1}}== | ==Trastuzumab deruxtecan monotherapy {{#subobject:ea894c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:98buya|Variant=1}}=== | ===Regimen {{#subobject:98buya|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 80%; text-align:center;" | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
Line 142: | Line 112: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*HER2 amplification | *HER2 amplification | ||
− | |||
''Diagnostic criteria for Her2 positivity in DESTINY-CRC01:'' | ''Diagnostic criteria for Her2 positivity in DESTINY-CRC01:'' | ||
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*Three cohorts were based on the degree of Her2 positivity: | *Three cohorts were based on the degree of Her2 positivity: | ||
**HER2-positive with immunohistochemistry (IHC) scoring 3+ or IHC 2+/in situ hybridization (ISH)+ (cohort A, n = 53) | **HER2-positive with immunohistochemistry (IHC) scoring 3+ or IHC 2+/in situ hybridization (ISH)+ (cohort A, n = 53) | ||
**HER2 IHC 2+/ISH– (cohort B, n = 7) | **HER2 IHC 2+/ISH– (cohort B, n = 7) | ||
**HER2 IHC 1+ (cohort C, n = 18). | **HER2 IHC 1+ (cohort C, n = 18). | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Antibody-drug conjugate therapy==== | ====Antibody-drug conjugate therapy==== | ||
− | |||
*[[Trastuzumab deruxtecan (Enhertu)]] 6.4 mg/kg IV once on day 1 | *[[Trastuzumab deruxtecan (Enhertu)]] 6.4 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- #'''Abstract:''' Siena S, Bartolomeo MD, Raghav KPS, Masuishi T, Loupakis G, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Saxena F, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, and Yoshino T. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. Journal of Clinical Oncology 2020 38:15_suppl, 4000-4000 [https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4000 link to abstract] --> | <!-- #'''Abstract:''' Siena S, Bartolomeo MD, Raghav KPS, Masuishi T, Loupakis G, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Saxena F, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, and Yoshino T. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. Journal of Clinical Oncology 2020 38:15_suppl, 4000-4000 [https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4000 link to abstract] --> | ||
#'''DESTINY-CRC01:''' Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779-789. Epub 2021 May 4. [https://doi.org/10.1016/s1470-2045(21)00086-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33961795/ PubMed] NCT03384940 | #'''DESTINY-CRC01:''' Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779-789. Epub 2021 May 4. [https://doi.org/10.1016/s1470-2045(21)00086-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33961795/ PubMed] NCT03384940 | ||
− | |||
==Tucatinib & Trastuzumab {{#subobject:ea8udc|Regimen=1}}== | ==Tucatinib & Trastuzumab {{#subobject:ea8udc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:98buya|Variant=1}}=== | ===Regimen {{#subobject:98buya|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 181: | Line 147: | ||
|} | |} | ||
''Note: dosing details are from the FDA labeling.'' | ''Note: dosing details are from the FDA labeling.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*HER2 amplification and KRAS wild-type | *HER2 amplification and KRAS wild-type | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
Line 189: | Line 158: | ||
*[[Tucatinib (Tukysa)]] 300 mg PO twice per day | *[[Tucatinib (Tukysa)]] 300 mg PO twice per day | ||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
#'''MOUNTAINEER:''' NCT03043313 | #'''MOUNTAINEER:''' NCT03043313 | ||
− | |||
[[Category:Colon cancer regimens]] | [[Category:Colon cancer regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Colorectal cancers]] | [[Category:Colorectal cancers]] |
Revision as of 13:03, 23 January 2023
Section editor transclusions Note: the page has regimens specific to Her2-amplified colon cancer.
- See the main colorectal cancer page for general regimens.
3 regimens on this page
2 variants on this page
|
Guidelines
ESMO
- 2016: Van Cutsem et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. PubMed
Older
- 2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines PubMed
- 2013: Balmaña et al. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. PubMed
Japanese Society for Cancer of the Colon and Rectum
- 2016: Watanabe et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer PubMed
NCCN
SIOG
- 2014: Papamichael et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013
Advanced or metastatic disease, second or third-line therapy
Pertuzumab & Trastuzumab
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Meric-Bernstam et al. 2019 (MyPathway HER2 CRC subset) | 2014-2017 | Phase 2 | ORR: 32% (95% CI 20-45%) |
Biomarker eligibility criteria
- HER2 amplification
Patients enrolled in MyPathway had ECOG 0-2 Diagnostic criteria for Her2 positivity in MyPathway:
- Patients with solid tumors that have HER2 overexpression, amplification, or HER2-activating mutation as identified by assays performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
- Assays using in situ hybridization (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) must indicate the presence of gene amplification with a HER2/CEP17 ratio of ≥ 2 or HER2 gene copy number > 6.0.
- Assays using IHC must indicate a score of 3 +.
- Assays using next generation sequencing (NGS) of genes with known or potentially clinically relevant alterations or analysis by real-time polymerase chain reaction (RT-PCR) must identify clinically activating mutations (those with major coding disruptions resulting in an amino acid change that is likely to be detrimental to protein function, including premature stop codons or frameshift mutations early in the coding region) or copy number gain.
- In cases where multiple assays are done, HER2 positivity by any of the testing methodologies would make the patient eligible as long as eligibility criteria are fulfilled.
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- MyPathway HER2 CRC subset: Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. Epub 2019 Mar 8. link to original article contains dosing details in manuscript PubMed NCT02091141
Lapatinib & Trastuzumab
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Sartore-Bianchi et al. 2016 (HERACLES) | 2012-2015 | Phase 2 | ORR: 30% (95% CI 14-50%) |
Biomarker eligibility criteria
- KRAS wild-type, HER2 amplification
Patients enrolled in HERACLES had ECOG 0-1 Diagnostic criteria for Her2 positivity in HERACLES:
- Tumours with 3+ HER2 score in more than 50% of cells by immunohistochemistry
or
- 2+ HER2 score and a HER2:CEP17 ratio higher than two in more than 50% of cells by FISH
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once per day
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1
7-day cycles
References
- HERACLES: Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):738-746. Epub 2016 Apr 20. link to original article PubMed EudraCT 2012-002128-33
Trastuzumab deruxtecan monotherapy
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Siena et al. 2021 (DESTINY-CRC01) | 2018-2019 | Phase 2 | ORR: 45% (95% CI 32-60%) |
Biomarker eligibility criteria
- HER2 amplification
Diagnostic criteria for Her2 positivity in DESTINY-CRC01:
- Three cohorts were based on the degree of Her2 positivity:
- HER2-positive with immunohistochemistry (IHC) scoring 3+ or IHC 2+/in situ hybridization (ISH)+ (cohort A, n = 53)
- HER2 IHC 2+/ISH– (cohort B, n = 7)
- HER2 IHC 1+ (cohort C, n = 18).
Antibody-drug conjugate therapy
- Trastuzumab deruxtecan (Enhertu) 6.4 mg/kg IV once on day 1
21-day cycles
References
- DESTINY-CRC01: Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779-789. Epub 2021 May 4. link to original article contains dosing details in abstract PubMed NCT03384940
Tucatinib & Trastuzumab
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Awaiting publication (MOUNTAINEER) | 2017-NR | Phase 2 (RT) |
Note: dosing details are from the FDA labeling.
Biomarker eligibility criteria
- HER2 amplification and KRAS wild-type
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
- Tucatinib (Tukysa) 300 mg PO twice per day
21-day cycles
References
- MOUNTAINEER: NCT03043313